Dysfunction of the thick loop of Henle and senescence: from molecular biology to clinical geriatrics

The sodium-potassium-2 chloride bumetanide-sensitive transporter (NKCC2), a protein coded by gene SLC12A1, allows salt reabsorption in the thick ascending loop of Henle (TALH). The functional and clinical exploration of the TALH can be carried out using the Chaimowitz's test, which is based on the exploration of the tubular response to an acute overload of a hypotonic sodium chloride solution. Since this segment is normally responsible for the generation of free water clearance, its function can be assessed via the calculation of such clearance from the parameters obtained during this test. By applying the Chaimowitz's test, the presence of incompetence for sodium reabsorption in TALH in healthy old people was documented. Additionally, it was documented that in water-restricted old rats, a situation that normally induces an increase in the number of NKCC2 in young rats is absent in old ones. In the clinical setting, the increased urinary sodium loss usually found in healthy old people predisposes them to dehydration, hypotension and or hyponatremia when they are on low-sodium diet or under treatment with diuretics. These are commonly found in elderly people with geriatric syndromes such as delirium, gait disorders and incontinence.

The NKCC2 transporter decrease in the thick ascending loop of Henle secondary to the ageing could explain the reduced sodium reabsorption of this segment in the healthy elderly and its potential clinical consequences of dehydration and serum sodium abnormalities.